Clinical analysis systems or analyzers having so-called “wet” chemistry systems require a sample supply for retaining a plurality of patient sample containers, at least one reagent supply containing at least one reagent, and at least one reaction containment device to carry out a wet assay. The reaction containment device can assume many different forms, but typically the device is either a cuvette containing a plurality of reaction chambers or a single reaction well. The assay is incubated during the formation thereof on an aliquot of sample which is combined, depending on the assay, with certain other fluids, such as reagents, and/or other substances to create some noticeable event, such as fluorescence or light absorbency. The event can subsequently be measured using a testing device, such as a spectrophotometer, colorimeter, reflectometer, electrometer, polarimeter, luminometer or other suitable device in order to detect the event and perform correlated analyte detection.
In chemistry systems of this type and particularly with immunoassays, multiple reagents and washing steps are required to prevent carryover. That is, whenever reagent metering involves aspirating and dispensing of different reagents, it is desirable to include at least one wash step so that the reagent metering probe does not carry over reagent from one step of an assay into a different step of an assay or into a different assay.
In general, a reagent probe is used to aspirate a quantity of reagent from a reagent supply, and then dispense the reagent into the reaction vessel. Following dispensing and prior to aspirating a new reagent, the probe must then be washed to avoid carryover. By “washing”, what is meant is that the reagent probe must be flushed with a wash fluid after delivery of each reagent component. The reagent probe is fluidly interconnected to a wash solution wherein the probe can be charged and dispense wash fluid by vacuum or pressure. The reagent wash station includes a wash cylinder which provides an enclosed space for the probe in order to conduct a wash step. In operation, the probe is lowered by conventional means into the wash cylinder of the wash station and wash fluid is charged through the probe and into the wash cylinder and evacuated through an outlet port. The wash fluid is also charged through an inlet port in order to wash the exterior of the probe.
The wash operation further requires the use of a fluid (wash) supply and associated tubing and pneumatic or other fluid delivery apparatus in order to direct wash fluid from the supply into the wash station. Similarly, waste wash fluid must be collected from the wash station and is directed through similar pneumatics or similar fluid delivery means to a waste supply. Typically, each of the wash supply and the waste supply are contained in bottle-like containers that are typically located in a lower cabinet of the analyzer housing.
A known example of the above form of analyzer is now more specifically described. In brief, the analyzer includes a housing having a set of reagent wells which are stacked in combination with a reagent supply containing a reagent. The reagent wells can be accessed selectively for test assays to be conducted.
Initially and according to the analyzer described herein, an empty reaction well is removed from a well supply and transferred into an incubator. The empty reaction well is shifted by known means of the incubator to a sample metering station within the incubator to receive metered sample. A conical metering tip located at a tip supply is collected by a metering mechanism, the conical tip being applied or otherwise attached to the end of a proboscis. Following attachment, the tip is transferred from the tip supply on a pivotal or linear metering arm retaining the proboscis to a primary sample supply having a plurality of primary tubular sample containers. The proboscis having the attached metering tip is lowered into a designated primary sample container and a volume of patient sample is aspirated into the tip. The tip is then raised from the primary patient container and the metering arm is moved to the sample metering position at the incubator. The tip is lowered into an opening provided in the incubator cover defining the sample metering station and sample is dispensed into the reaction well. Following the above metering step, the used metering tip is stripped from the proboscis and is discarded at a dump station.
The reaction well is then further incubated within the incubator to a reagent metering position. In this position, the reagent probe is brought to a first reagent container and a volume of reagent fluid is aspirated from the container into the probe. The probe is then pivoted to the incubator, lowered into the reagent metering position, and dispenses the reagent into the reaction well. The probe is not placed into contact with the sample fluid already contained within the reaction well. Rather, the reagent is injected at high velocity into the reaction well to induce mixing. In addition, the incubator includes a vibratory bed which further promotes mixing to occur.
The reagent probe is then raised from the incubator and pivoted to a wash station, such as shown in FIG. 1. As previously noted, the wash station 210 includes a wash cylinder 215 which provides an enclosed space and into which the reagent probe 200 is positioned. Wash liquid from a wash liquid supply (not shown) is charged both into the interior of the reagent probe 200 and along the exterior of the reagent probe 200 through an inlet port 220 by means of an elaborate pneumatic system (not shown) having at least one pump as well as sufficient valving and tubing for fluidly directing wash liquid from the wash liquid supply. Waste liquid is directed through the contents of the reagent probe 200 to an outlet port 224 and subsequently by means of a separate pneumatic/fluidic system (not shown) to a waste chamber (not shown) provided at the bottom of the analyzer housing in a dedicated cabinet (not shown).
Depending on the assay, the reaction well is then further incremented within the incubator to a second reagent metering position. At this position, the reagent probe is shuttled to the second reagent supply and a suitable volume of second reagent is aspirated into the probe for reaction probe is again positioned by the metering system to the wash station and the preceding wash steps are repeated. Additional reagents can be added, again depending on the type of assay.
The sample fluid and reagents are then incubated together. In the example herein described, the reaction well may include a bonded antibody layer. If luminescent tests are required for the assay, the contents of the reaction well must first be washed in order to remove the fluid contents through a series of washing and suction steps. The remaining bound material then receives a signal generating reagent prior to testing using a luminometer. Chemiluminescent signals generated by the reagent/sample combination are transmitted to a photo multiplier which converts the light signal into an electrical signal for processing according to conventional digital techniques. The signal generating agent is dispensed using the reagent probe as previously described or pumped directly from bottles. The reagent probe is washed following dispensing of the reagent to the reaction well.
Alternately, and if light absorbency testing is required, then the reagent/sample fluid combination contained in the reaction well is tested using an optical testing device, such as a spectrophotometer. Additional details relating to the wash-related steps and the preparation of assays using the above analyzer are provided in U.S. application Ser. No. 09/482,599, entitled: FAILURE DETECTION IN AUTOMATED CLINICAL ANALYZERS, the entire contents of which are incorporated by reference.
It should be further noted that additional problems in addition to those relating to the overall cost and complexity of providing wash apparatus to a clinical analyzer include potential risks of cross contamination of fluids, particularly reagents given that reagent packs can include multiple adjacent bottles, each bottle having a different reagent.
There is a generally recognized need in the field to eliminate or substantially reduce the complexity of clinical analytical systems in which assays, such as described above, are conducted.